@article{d328996e8ecc4600b3e288bd3ca7d499,
title = "Recapitulation of treatment response patterns in a novel humanized mouse model for chronic hepatitis B virus infection",
abstract = "There are ~350 million chronic carriers of hepatitis B (HBV). While a prophylactic vaccine and drug regimens to suppress viremia are available, chronic HBV infection is rarely cured. HBV's limited host tropism leads to a scarcity of susceptible small animal models and is a hurdle to developing curative therapies. Mice that support engraftment with human hepatoctyes have traditionally been generated through crosses of murine liver injury models to immunodeficient backgrounds. Here, we describe the disruption of fumarylacetoacetate hydrolase directly in the NOD Rag1-/- IL2RγNULL (NRG) background using zinc finger nucleases. The resultant human liver chimeric mice sustain persistent HBV viremia for >90 days. When treated with standard of care therapy, HBV DNA levels decrease below detection but rebound when drug suppression is released, mimicking treatment response observed in patients. Our study highlights the utility of directed gene targeting approaches in zygotes to create new humanized mouse models for human diseases.",
keywords = "Antivirals, Genome engineering, Hepatitis B virus (HBV), Humanized mice",
author = "Winer, {Benjamin Y.} and Tiffany Huang and Pais, {Mihai Alexandru} and Gabriela Hrebikova and Evelyn Siu and Alexander Ploss and Low, {Benjamin E.} and Cindy Avery and Wiles, {Michael V.} and Luis Chiriboga",
note = "Funding Information: HepG2.2.15 cells were kindly provided by Christoph Seeger (Fox Chase Cancer Center). We would like to thank Rosalinda Doty for her skillful pathology work and Jenna Gaska for her helpful discussions and edits of this manuscript. We would also like to thank Gabriel Lipkowitz for his assistance with experiments. This study is supported by grants from the National Institutes of Health (R01 AI079031, R01 AI107301, R21AI117213 to AP), a Research Scholar Award from the American Cancer Society (RSG-15-048-01-MPC to AP), a Burroughs Wellcome Fund Award (1015389), for Investigators in Pathogenesis (to AP) and a Health Grand Challenge Graduate fellowship from the Global Health Fund of Princeton University (to BYW). The NYU Experimental Pathology Immunohistochemistry Core Laboratory is supported in part by the Laura and Isaac Perlmutter Cancer Center Support Grant; NIH /NCI P30CA016087” and the National Institutes of Health S10 Grants; NIH/ORIP S10OD01058 and S10OD018338. BYW is a recipient of F31 NIH/NRSA Ruth L. Kirschstein Predoctoral awarded from the NIAID, MVW, CA and BEL were funded by The Jackson Laboratory. MAP was supported by a fellowship from Evangelisches Studienwerk Villigst. Publisher Copyright: {\textcopyright} 2016",
year = "2017",
month = feb,
day = "1",
doi = "10.1016/j.virol.2016.12.017",
language = "English (US)",
volume = "502",
pages = "63--72",
journal = "Virology",
issn = "0042-6822",
publisher = "Academic Press Inc.",
}